Modeling the Lifetime Impact of Reconstructive Plastic Surgery Training: Implications for Building Capacity in Global Surgery.

Background: Training local surgeons and building local surgical capacity is critical to closing the gap in unmet surgical burden in low- and middle-income country (LMIC) settings. We propose a conceptual framework to quantify the impact of a single surgeon's training across multiple generations of trainees. Methods: A literature review was conducted to identify existing models for quantifying the impact of training. A model to estimate the attributable impact of surgical training was devised, based on a surgeon's attributable impact on a trainee and the lifetime number of cases trainees would perform. A quantitative survey was sent to high-income country and LMIC-based surgeons to determine the model's inputs across eight index procedures in reconstructive plastic surgery. Results: We found no existing models for quantifying the multigenerational impact of training in surgery, medicine, or nonmedical fields. Twenty-eight US-based academic plastic surgeons and 19 LMIC-based surgeons representing 10 countries provided responses. The lifetime impact of multigenerational surgical training ranged from 4100 attributable cases (skin graft) to 51,900 attributable cases (cleft lip repair) in high-income countries and from 18,200 attributable cases (carpal tunnel release) to 134,300 attributable cases (cleft lip repair) in LMICs. Conclusions: There is a sizeable impact in the first generation of training, and this impact is even greater in the second generation of training, highlighting the importance of a "multiplier effect," particularly in LMIC settings. Given the paucity of surgeons, this multiplier effect is critical in closing the surgical gap, as efforts are underway to train new cohorts of reconstructive plastic surgeons.

Improving Operating Room Efficiency Through Reducing First Start Delays in an Academic Center.

BACKGROUND: Delays in operating room (OR) first-case start times can cause additional costs for hospitals, healthcare team frustration and delay in patient care. Here, a novel process improvement strategy to improving first-case start times is presented. METHODS: First case in room start times were recorded for ORs at an academic medical center. Three interventions-automatic preoperative orders, dot phrases to permit re-creation of unavailable consent forms, and improved H&P linking to the surgical encounter-were implemented to target documentation-related delays. Monthly percentages of first-case on-time starts (FCOTS) and time saved were compared with the "preintervention" time period, and total cost savings were estimated. RESULTS: During the first 3-months after implementation of the interventions, the percentage of FCOTS improved from an average of 36.7%-52.7%. Total time savings across all ORs over the same time period was found to be 55.63 hours, which is estimated to have saved a total of $121,834.52 over the 3-month interventional period. CONCLUSIONS: By implementing multiple quality improvement interventions, delays to first start in room OR cases can be meaningfully reduced. Quality improvement protocols targeted toward root causes of OR delays can be a significant driver to reduce healthcare costs.

Characterizing Clinical Trials in Plastic and Reconstructive Surgery: A Systematic Review of ClinicalTrials.gov From 2007 to 2020.

BACKGROUND: Clinical trials form the backbone of evidence-based medicine. ClinicalTrials.gov is the world's largest clinical trial registry, and the state of clinical trials in plastic and reconstructive surgery (PRS) within that database has not been comprehensively studied. To that end, we explored the distribution of therapeutic areas that are under investigation, impact of funding on study design and data reporting, and trends in research patterns of all PRS interventional clinical trials registered with ClinicalTrials.gov. METHODS: Using the ClinicalTrials.gov database, we identified and extracted all clinical trials relevant to PRS that were submitted between 2007 and 2020. Studies were classified based on anatomic locations, therapeutic categories, and specialty topics. Cox proportional hazard was used to calculate adjusted hazard ratios (HRs) for early discontinuation and results reporting. RESULTS: A total of 3224 trials that included 372,095 participants were identified. The PRS trials grew at an annual rate of 7.9%. The therapeutic classes most represented were wound healing (41.3%) and cosmetics (18.1%). Funding for PRS clinical trials is largely provided through academic institutions (72.7%), while industry and US government constituted a minority. Industry-funded studies were more likely to be discontinued early than those funded by academics (HR, 1.89) or government (HR, 1.92) and to be nonblinded and nonrandomized. Academic-funded studies were the least likely to report results data within 3 years of trial completion (odds ratio, 0.87). CONCLUSIONS: A gulf exists in the representation of different PRS specialties among clinical trials. We highlight the role of funding source in trial design and data reporting to identify a potential source of financial waste and to stress the need for continued appropriate oversight.

Risk stratification in subpectoral to prepectoral pocket conversion to reduce post-reconstruction animation deformity.

BACKGROUND: Animation deformity is a morbid complication that impacts women undergoing subpectoral implant-based breast reconstruction. Transferring implants from the subpectoral to prepectoral space, pocket conversion, can be performed to minimize this issue. While prior literature has evaluated outcomes associated with this procedure, we investigated the risk factors most commonly associated with post-conversion complications. METHODS: We performed a retrospective cohort investigation of women undergoing prepectoral pocket conversion. Pre-conversion clinical characteristics and surgical complications (major and minor) were collected. Predictors for postoperative complications were identified using univariate and multivariate logistic regression models. Odds ratios (OR) and adjusted odds ratios (aOR) are presented with 95% confidence intervals, and p-values were assessed at α = 0.05. RESULTS: A total of 34 patients (63 breasts) were included. Pocket conversion relieved animation deformity in all breasts. The overall rates of major and minor complications were 14.3% (n = 9/63) and 34.9% (n = 22/63), respectively, by mean follow-up of 11.1 months. After adjusting for confounders, pre-conversion implant rupture (OR= 6.00, CI= 0.99-34.58; aOR= 12.8, CI= 1.15-170.32) and duration of implant placement (OR=1.35, CI= 1.07-1.78; aOR= 1.1, CI= 1.00-1.21) were found to be significant predictors of major postoperative complications. CONCLUSION: With a fairly inclusive patient population, this series provides data for improved risk stratification of patients considering conversion to relieve animation deformity. Interestingly, traditional risk factors (namely, body mass index and smoking status) were not significant predictors for postoperative complications, suggesting that conversion may be safe in high-risk patients. Such data support more informed preoperative counseling and wider application of this procedure.

Does Higher Intraoperative Fraction of Inspired Oxygen Improve Complication Rates Following Implant-Based Breast Reconstruction?

Background: The surgical literature debates about whether an average intraoperative fractional inspired level of oxygen (FiO2) greater than 80% confers lower postsurgical complication rates. Although some evidence demonstrates minimal or no difference in short-term mortality or surgical site infections, few studies suggest negative long-term outcomes. Objectives: To the best of our knowledge, this is the first study examining the relationship between intraoperative FiO2 levels and postoperative outcomes in the setting of immediate prepectoral implant-based breast reconstruction. Methods: The authors retrospectively reviewed the complication profiles of 309 patients who underwent prepectoral 2-stage breast reconstruction following mastectomy between 2018 and 2021 at a single institution. Two cohorts were created based on whether intraoperative FiO2 was greater than 80% or less than or equal to 80%. Complication rates between the cohorts were analyzed using Chi-squared test, Fisher's exact test, and multivariable logistic regressions. Variables examined included demographic information; smoking history; preexisting comorbidities; history of chemotherapy, radiation, or axillary lymph node dissection; and perioperative information. Results: Chi-squared and multivariable regression analysis demonstrated no significant difference between cohorts in complication rates other than reoperation. Reoperation rates were significantly increased in the FiO2 greater than 80% cohort (P = 0.018). Multivariable logistic regression also demonstrated that the use of acellular dermal matrix was significantly associated with increased postoperative complications (odds ratio 11.985; P = 0.034). Conclusions: Complication rates did not statistically differ in patients with varying intraoperative FiO2 levels outside of reoperation rates. In the setting of implant-based prepectoral breast reconstruction, hyperoxygenation likely does not lead to improved postsurgical outcomes.

The Impact of Reconstructive Modality and Postoperative Complications on Decision Regret and Patient-Reported Outcomes following Breast Reconstruction.

Shared decision-making gives patients greater autonomy in their healthcare decisions; however, decisions that result in negative outcomes may lead to decision regret. The complexity of reconstructive options makes post-mastectomy breast reconstruction particularly prone to decision regret. This study's purpose was to explore the relationship between breast reconstruction modalities and degree of postoperative decision regret. Patients who had undergone either implant-based or autologous breast reconstruction with a minimum of 12 months of follow-up were invited to complete the Decision Regret Scale and the BREAST-Q Satisfaction with Breasts module. The impact of reconstructive modality and occurrence of postoperative complications on decision regret and satisfaction with breasts was examined. Sixty-three patients completed the questionnaires-25 patients with implant-based reconstruction and 38 patients with autologous reconstruction. The average Decision Regret score was 84.6 ± 23.6; thirty-one patients experienced no decision regret. The average score for the BREAST-Q module was 81.9 ± 18.8. Neither satisfaction with breasts nor decision regret were impacted by the reconstructive modality. The occurrence of postoperative complications was strongly correlated with lower Decision Regret scores (91.6 vs. 74.6, p=0.004) but was not correlated with lower Satisfaction with Breasts scores (84.6 vs. 78.2, p=0.18). Patients had relatively low levels of decision regret and relatively high levels of satisfaction with breasts, irrespective of reconstructive modality. Having a postoperative complication led to significantly greater levels of decision regret without impacting satisfaction with breasts. Patients may benefit from additional preoperative education on possible complications to mitigate decision regret. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Maintaining Contour with a Three-dimensional Interstitial Tissue Marker in 134 Lumpectomies.

Breast-conserving surgery (BCS) is meant to preserve the natural appearance of the breast; however, tissue volume deficits cannot always be compensated by soft tissue mobilization. A three-dimensional (3D) interstitial tissue marker (BioZorb) was designed to delineate the lumpectomy cavity for targeting boost irradiation, but an unexpected secondary benefit may be in guiding wound contraction and restoring contour to the lumpectomy bed. We analyze tissue volume excised at the time of lumpectomy as a function of device size selected. METHODS: In total, 134 consecutive lumpectomy patients implanted with BioZorb between May 2015 and February 2020 were retrospectively analyzed for tissue volume excised, device size used, location, and re-operation rates, including explantation of the device. RESULTS: An estimated 113 patients underwent device implantation at initial lumpectomy, and 21 at margin re-excision. Twenty-seven patients underwent re-excision, while 14 elected mastectomy for positive margins following insertion; 22 had the same device reimplanted. Mean lumpectomy volume was 79.0 cm3 (range 10.3-275.8 cm3) during the first implant procedure. Large-volume lumpectomies, averaging 136.5 cm3, were associated with selection of larger devices, which aided in restoring volume and maintaining breast contour. Three (2.2%) patients requested removal of the device. CONCLUSIONS: BioZorb implantation can be a safe and useful oncoplastic technique for restoring volume with BCS. Large-volume lumpectomies can be performed without contouring defects using the device. An unexpected secondary benefit of the device may be scaffolding for wound contraction.

Autologous Fat Grafting and the Occurrence of Radiation-Induced Capsular Contracture.

INTRODUCTION: Radiation therapy is a known risk factor for capsular contracture formation after implant-based breast reconstruction. Although autologous fat grafting (AFG) has been shown to reverse radiation-induced tissue fibrosis, its use as a prophylactic agent against capsular contraction has not been assessed in the clinical setting. In the setting of 2-stage implant-based reconstruction and postmastectomy radiation therapy, we explored the effect AFG has on the prevalence of capsular contracture. MATERIALS AND METHODS: A retrospective chart review of patients who underwent immediate tissue expander (TE) placement followed by postmastectomy radiation therapy and secondary implant-based reconstruction at our institution between January 2012 and December 2019 was performed. Patients were divided into 2 cohorts based on whether or not AFG was performed at the time of secondary reconstruction. The primary outcome of interest was the occurrence of capsular contracture after TE exchange. RESULTS: Overall 57 patients (57 breasts) were included, 33 of whom received AFG at the time of TE exchange. All but 1 patient underwent submuscular implant placement, and the mean follow-up was 1.96 years. There was no significant difference in the prevalence of medical comorbidities between the study groups.Capsular contracture occurred in 24 patients (42.1%). Seventeen of these patients had undergone AFG at the time of TE exchange (17/33 patients, 51.5%), and 7 of these patients had not (7/24 patients, 29.2%). Most of the capsular contracture cases were Baker grades III or IV (14 patients, 58.3%), and 50% of patients with capsular contracture of any grade ultimately required operative intervention. Multivariate logistic regression analysis demonstrated that AFG did not significantly influence the occurrence or severity of capsular contracture, or did not impact the need for operative intervention in this patient population. CONCLUSIONS: Implant-based reconstruction of the irradiated breast is associated with high postoperative capsular contracture rates. Although AFG has shown promise in reversing radiation-induced dermal fibrosis, no protective effect on the development of capsular contracture after stage 2 reconstruction was observed in this study population. Further investigation in the form of randomized, prospective studies is needed to better assess the utility of AFG in preventing capsular contracture in irradiated patients.

Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part.

Cardiac development is a dynamic process, temporally and spatially. When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor NKX2-5 being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an Nkx2-5 mutation. Intermittent mild hyperoxia (40% PO2) was applied for 10 h per day to normal wild-type female mice mated with heterozygous Nkx2-5 mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in Nkx2-5 mutant mice compared to normoxic conditions (ratio of trabecular layer relative to compact layer area, normoxia 1.84 ± 0.07 vs. hyperoxia 1.51 ± 0.04) and frequency of muscular ventricular septal defects per heart (1.53 ± 0.32 vs. 0.68 ± 0.15); however, the incidence of membranous ventricular septal defects in Nkx2-5 mutant hearts was not changed. Nkx2-5 mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by Nkx2-5 mutation in part.

Left Atrial Strain Is the Best Predictor of Adverse Cardiovascular Outcomes in Patients with Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk of adverse cardiovascular events, which is underestimated by traditional risk stratification algorithms. We sought to determine clinical and echocardiographic predictors of adverse outcomes in CKD patients. METHODS: Two hundred forty-three prospectively recruited stage 3/4 CKD patients (male, 63%; mean age, 59.2 ± 14.4 years) without previous cardiac disease made up the study cohort. All participants underwent a transthoracic echocardiogram, with left ventricular (LV) and left atrial (LA) strain analysis. Participants were followed for 3.9 ± 2.7 years for the primary end point of cardiovascular death and major adverse cardiovascular event (MACE). The secondary end point was the composite of all-cause death and MACE. RESULTS: Fifty-four patients met the primary end point, and 65 the secondary end point. On log-rank tests, older age, diabetes mellitus, anemia, greater LV mass, reduced LV global longitudinal strain, larger indexed LA volume, higher E/e' ratio, and reduced LA reservoir strain (LASr; P < .01 for all) were independent predictors of cardiovascular death and MACE. On multivariable regression analysis of univariate predictors, LASr (P < .01) was the only independent predictor for the primary end point as well as for the secondary end point. Receiver operating characteristic curve analysis showed LASr was a stronger predictor of adverse events (area under the curve [AUC] = 0.84) compared to the Framingham (AUC = 0.58) and Atherosclerotic Cardiovascular Disease (AUC = 0.59) risk scores. CONCLUSIONS: LASr is an independent predictor of cardiovascular death and MACE in CKD patients, superior to clinical risk scores, LV parameters, and LA volume.

Comparing Prepectoral Versus Subpectoral Tissue Expander Placement Outcomes in Delayed-Immediate Autologous Breast Reconstruction.

BACKGROUND: Delayed-immediate breast reconstruction has traditionally involved placement of tissue expanders (TE) in the subpectoral (SP) position. Development of acellular dermal matrices has renewed interest in the prepectoral (PP) pocket, which avoids extensive muscle manipulation. We compare complication rates between PP and SP TE placement in autologous delayed-immediate breast reconstruction. METHODS: A retrospective chart review of patients undergoing autologous, delayed-immediate breast reconstruction at our institution (June 2009 to December 2018) was performed. Demographics, comorbidities, perioperative information, and complication incidence ≤12 months' follow-up were collected from first- and second-stage surgeries. Complications were modeled using univariable and multivariable binary logistic regressions. RESULTS: A total of 89 patients met the inclusion criteria, and data from 125 breast reconstructions were evaluated. Complication rates following TE placement trended lower in the PP cohort (28.8% vs 37%, P = 0.34). Overall complication rates following autologous reconstruction were significantly lower for PP reconstructions (7.7% vs 23.3%, P = 0.02). Multivariable regression showed TE position (P = 0.01) was a significant predictor of ≥1 complication following autologous reconstruction. Time delay between first- and second-stage surgeries was greater for SP reconstructions (199.7 vs 324.8 days, P < 0.001). Postoperative drains were removed earlier in the PP cohort (8.6 vs 12.0 days, P < 0.001). Mean follow-up time was 331.3 days. CONCLUSIONS: Prepectoral reconstruction in the delayed-immediate autologous reconstruction patient leads to significantly lower complication rates, shorter duration between first- and second-stage surgeries, and shorter times before removal of breast drains compared with SP reconstructions.

Defective coronary vessel organization and reduction of VEGF-A in mouse embryonic hearts with gestational mild hypoxia.

BACKGROUND: Vasculature is formed by responding to homeostatic tissue demands including in developing hearts. Hypoxia generally stimulates vascular formation in which vascular endothelial growth factor A (VEGF-A) plays a critical role. Gestational hypoxia increases the risk of low intrauterine growth and low birth weight, both of which are known to increase the risk of the fetus developing cardiovascular defects. In fact, continuous gestational mild hypoxia (14% O2 ) from the mid-embryonic stage causes cardiac anomalies accompanied by a thinning compact layer in mice in vivo. Because coronary vasculature formation is necessary for compact layers to thicken, we hypothesized that defective coronary vessel organization is related to the thinning compact layer under gestational hypoxia conditions. RESULTS: Continuous gestational mild hypoxia (14% O2 ) applied from embryonic day 10.5 (E10.5) reduced the expression of VEGF-A mRNA and proteins by over 60% in E12.5 hearts relative to control normoxic hearts. Formation of CD31-positive vascular plexus, blood islands, and microvessels in embryonic ventricles were stunted by gestational hypoxia compared to control E12.5 hearts. CONCLUSIONS: Our results suggest that mild hypoxia (14% O2 ) does not induce coronary vessel organization or VEGF-A expression in developing mouse hearts, opposing the general effects of hypoxia-triggering vascular organization and VEGF-A expression.

Cardiac MLC2 kinase is localized to the Z-disc and interacts with α-actinin2.

Cardiac contractility is enhanced by phosphorylation of myosin light chain 2 (MLC2) by cardiac-specific MLC kinase (cMLCK), located at the neck region of myosin heavy chain. In normal mouse and human hearts, the level of phosphorylation is maintained relatively constant, at around 30-40% of total MLC2, likely by well-balanced phosphorylation and phosphatase-dependent dephosphorylation. Overexpression of cMLCK promotes sarcomere organization, while the loss of cMLCK leads to cardiac atrophy in vitro and in vivo. In this study, we showed that cMLCK is predominantly expressed at the Z-disc with additional diffuse cytosolic expression in normal adult mouse and human hearts. cMLCK interacts with the Z-disc protein, α-actinin2, with a high-affinity kinetic value of 13.4 ± 0.1 nM through the N-terminus region of cMLCK unique to cardiac-isoform. cMLCK mutant deficient for interacting with α-actinin2 did not promote sarcomeric organization and reduced cardiomyocyte cell size. In contrast, a cMLCK kinase-deficient mutant showed effects similar to wild-type cMLCK on sarcomeric organization and cardiomyocyte cell size. Our results suggest that cMLCK plays a role in sarcomere organization, likely distinct from its role in phosphorylating MLC2, both of which will contribute to the enhancement of cardiac contractility.

The Golden Hour After Injury Among Civilians Caught in Conflict Zones.

INTRODUCTION: The term "golden hour" describes the first 60 minutes after patients sustain injury. In resource-available settings, rapid transport to trauma centers within this time period is standard-of-care. We compared transport times of injured civilians in modern conflict zones to assess the degree to which injured civilians are transported within the golden hour in these environments. METHODS: We evaluated PubMed, Ovid, and Web of Science databases for manuscripts describing transport time after trauma among civilian victims of trauma from January 1990 to November 2017. RESULTS: The initial database search identified 2704 abstracts. Twenty-nine studies met inclusion and exclusion criteria. Conflicts in Yugoslavia/Bosnia/Herzegovina, Syria, Afghanistan, Iraq, Israel, Cambodia, Somalia, Georgia, Lebanon, Nigeria, Democratic Republic of Congo, and Turkey were represented, describing 47 273 patients. Only 7 (24%) manuscripts described transport times under 1 hour. Transport typically required several hours to days. CONCLUSION: Anticipated transport times have important implications for field triage of injured persons in civilian conflict settings because existing overburdened civilian health care systems may become further overwhelmed if in-hospital health capacity is unable to keep pace with inflow of the severely wounded.

Heterozygous Mylk3 Knockout Mice Partially Recapitulate Human DCM With Heterozygous MYLK3 Mutations.

Backgrounds: Recent studies identified heterozygous variants in MYLK3 gene that encodes cardiac myosin light chain kinase (cMLCK) are related to familial dilated cardiomyopathy (DCM) for the first time. Autosomal dominant traits suggest that pathogenesis of DCM could be related to heterozygous MYLK3 loss-of-function variants (haploinsufficiency). We previously generated and examined homozygous Mylk3 knockout mice that lead to heart failure. It had yet to be examined whether heterozygous Mylk3 knockout mice represent a DCM-like phenotype. Methods and Results: Heterozygous knockout (Mylk3 wild/-) mice were examined regarding cardiac function, heart histology and expression of cMLCK protein and mRNA relative to age-matched wild-type controls (Mylk3 wild/wild). At 4 months of age, cardiac contractility in heterozygous knockout mice was reduced with percent fractional shortening of 23.3 ± 1.2% compared to 30.1 ± 1.8% in control (Mylk3 wild/- vs. Mylk3 wild/wild, n = 9 each). In 4-month-old heterozygous knockout hearts, expression of cMLCK mRNA was expectedly reduced by almost half, however, protein expression was reduced by approximately 75% relative to the control wild-type (Mylk3 wild/- vs. Mylk3 wild/wild, n = 9 each). Isolated ventricular cardiomyocytes from heterozygous knockout mice were larger with increase of short-axis length relative to the cardiomyocytes from control mice. However, increase of heart failure markers as well as interstitial fibrosis were not evident in heterozygous knockout mice compared to controls. Conclusion: Heterozygous Mylk3 knockout mice show mild reduction of cardiac contractility by 4 months of age, and proteins reduced by approximately 75% relative to the control wild-type mice. These mice partly resemble human with the heterozygous MYLK3 mutation, but the reduction in cardiac contractility was milder.